Toxic Shock Syndrome

Practice Essentials

Toxic shock syndrome (TSS) is a rare acute life-threatening illness, caused by a toxin-mediated infectious process linked to toxin-producing strains of Staphylococcus aureus or group A Streptococcus (GAS), also called Streptococcus pyogenes. TSS is characterized by high fever, rash, desquamation of palms and soles, hypotension, refractory shock, multiorgan failure, and death. The clinical syndrome can also include severe myalgia, vomiting, diarrhea, headache, and nonfocal neurologic abnormalities

See the image below.

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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteris....

TSS was first described in children in 1978.^[1]  Subsequent reports identified an association with tampon use by menstruating women.^{[2, 3, 4]}  Menstrual TSS is more likely in women using highly absorbent tampons, using tampons for more days of their cycle, and keeping a single tampon in place for a longer period of time. Over the past decades, the number of cases of menstrual TSS (0.5-1.0 per 100,000 population) has steadily declined; this is thought to be due to the withdrawal of highly absorbent tampons from the market.^[5]

Notably, 50% of cases of TSS are not associated with menstruation. Nonmenstrual cases of TSS usually complicate the use of barrier contraceptives, surgical and postpartum wound infections, burns, cutaneous lesions, osteomyelitis, and arthritis. Although most cases of TSS occur in women, about 25% of nonmenstrual cases occur in men.

In the 1980s, Cone initially reported and Stevens subsequently characterized GAS as a pathogen responsible for invasive soft tissue infection ushered by toxic shock–like syndrome.^{[6, 7]}  The streptococcal TSS is similar to staphylococcal TSS; however, the blood cultures usually are positive for staphylococci in TSS. Toxin-producing strains of S aureus infect or colonize people who have risk factors for the development of the syndrome. Most cases are related to the staphylococcal toxin, now called TSS toxin-1 (TSST-1).

GAS is an aerobic gram-positive organism that forms chains and is an important cause of soft tissue infections. Diabetes, alcoholism, varicella infections, and surgical procedures all increase the risk of severe GAS infections and hence may potentially increase the risk of TSS. Severe, invasive GAS infections can cause necrotizing fasciitis and spontaneous gangrenous myositis. An increasing number of severe GAS infections associated with shock and organ failure have been reported. These infections are termed streptococcal TSS (STSS).^[8]  See the image below.

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Description of M proteins and streptococcal toxins.

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Pathophysiology

TSS is linked mostly to toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus). These toxins act as superantigens in inducing nonclassic activation of T cells by antigen-presenting cells (APCs), leading to nonspecific, polyclonal lymphocyte activation of 5-30% of the total population of T cells, which results in massive release of proinflammatory cytokines.^[8]

The most commonly implicated toxins include TSS toxin type-1 (TSST-1) and staphylococcal enterotoxin B.

Almost all cases of menstrual TSS and half of all nonmenstrual cases are caused by TSST-1. Staphylococcal enterotoxin B is the second leading cause of TSS. Other exotoxins such as enterotoxins A, C, D, E, and H contribute to a small number of cases. Seventy to 80% of individuals develop antibody to TSST-1 by adolescence, and 90-95% have such antibody by adulthood. Apart from host immunity status, host-pathogen interaction, local factors (pH, glucose level, magnesium level), and age all have a direct impact on the clinical expression of this toxin-mediated illness.

M protein is an important virulent determinant of GAS; strains lacking M protein are less virulent. M protein is a filamentous protein anchored to the cell membrane, which has antiphagocyte properties. M protein types 1, 3, 12, and 28 are the most common isolates found in patients with shock and multiorgan failure; furthermore, three distinct streptococcal pyrogenic exotoxins (A, B, C) also have been identified. 

Mechanism of shock and tissue destruction

Colonization or infection with certain strains of S aureus and GAS is followed by the production of one or more toxins. These toxins are absorbed systemically and produce the systemic manifestations of TSS in people who lack a protective antitoxin antibody. Possible mediators of the effects of the toxins are cytokines, such as interleukin 1 (IL-1) and tumor necrosis factor (TNF). Pyrogenic exotoxins induce human mononuclear cells to synthesize TNF-alpha, IL-1-beta, and interleukin 6 (IL-6). 

Toxins produced by strains of S aureus and GAS act as superantigens. These superantigens interact and activate large numbers of T cells resulting in massive cytokine production.

Normally, an antigen has to be taken up, processed by an antigen-presenting cell, and expressed at the cell surface along with class II major histocompatibility complex (MHC). By contrast, superantigens do not require processing by antigen-presenting cells but instead interact directly with the class II MHC molecule. The superantigen-MHC complex then interacts with the T-cell receptor and stimulates large numbers of T cells to cause an exaggerated, dysregulated cytokine response. Massive production of cytokines leads to refractory shock and tissue injury.

As part of this unusual T cell response, interferon-gamma is also produced, which subsequently inhibits polyclonal immunoglobulin production. This failure to develop antibodies may explain why some patients are predisposed to relapse after a first episode of TSS.

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Etiology

Acquisition of infection

Risk factors for the development of  staphylococcal TSS are tampon use, vaginal colonization with toxin-producing S aureus, and lack of serum antibody to the staphylococcal toxin.^[9] Staphylococcal TSS also has occurred following use of nasal tampons for procedures of the ears, nose, and throat.

The portal of entry for streptococci is unknown in almost one half of the cases. Procedures such as suction lipectomy, hysterectomy, vaginal delivery, and bone pinning have been identified as the portal of entry in many cases. Most commonly, infection begins at a site of minor local trauma, which may be nonpenetrating. Viral infections, such as varicella and influenza, also have provided a portal of entry.

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Epidemiology

US frequency

Estimates from population-based studies have documented an incidence of invasive GAS infection of 1.5-5.2 cases per 100,000 people annually.^[10] Approximately 8-14% of these patients also will develop TSS.^[11] A history of recent varicella infection markedly increases the risk of infection with GAS to 62.7 cases per 100,000 people per year.  Severe soft tissue infections, including necrotizing fasciitis, myositis, or cellulitis, were present in approximately half of the patients.

Staphylococcal TSS is much more common, although data on prevalence do not exist. In the United States, from 1979-1996, 5296 cases of  staphylococcal TSS were reported. The incidence of menstrual TSS is currently estimated to be 0.5-1.0 per 100,000 population.^[5] The incidence of nonmenstrual TSS now exceeds menstrual TSS after the hyperabsorbable tampons were removed from the market.

Race

TSS has occurred in all races, although most cases have been reported from North America and Europe.

Sex

Staphylococcal TSS most commonly occurs in women, usually those who are using tampons.

Age

Some studies have shown no predilection for any particular age for either the streptococcal TSS or staphylococcal TSS. However, other studies have reported  staphylococcal TSS to be more common in older individuals with underlying medical problems. In a Canadian survey, staphylococcal TSS accounted for 6% of cases in individuals younger than 10 years compared with 21% in people older than 60 years.^[10] Furthermore, menstruation-associated  staphylococcal TSS occurred in younger women who were using tampons.

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Prognosis

The vast majority of patients with staphylococcal toxic shock syndrome (TSS) recover uneventfully. The mortality rate for staphylococcal TSS is approximately 5%.^[12]  Since the discontinuation of hyperabsorbable tampons, mortality is rare in patients with menstrual TSS. Contou et al did not report any deaths in a retrospective study of 120 women diagnosed with menstrual TSS between 2005 and 2020.^[13] Staphylococcal toxic shock syndrome can recur, particularly in the absence of antistaphylococcal therapy and with continued use of tampons. Neuropsychiatric manifestations, such as memory loss and lack of concentration, may persist in some patients.

A retrospective study conducted in a pediatric intensive care unit in India reported a mortality of 27% among children admitted with staphylococcal TSS. The patients in the study who did not survive were more likely to have central nervous system involvement, transaminitis, thrombocytopenia, coagulopathy, and acute kidney injury and to require mechanical ventilation and blood products.^[14]

Streptococcal TSS is associated with poorer outcomes than staphylococcal TSS. Mortality rates for streptococcal TSS are 30-70%.^{[15, 16]}  Morbidity also is high for streptococcal TSS; in one series, 13 of 20 patients underwent major surgical procedures, such as fasciotomy, surgical debridement, laparotomy, amputation, or hysterectomy.^[15]

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History

Although the clinical manifestations of toxic shock syndrome (TSS) can be diverse, the possibility of toxic shock should be considered in any individual who presents with sudden onset of fever, rash, hypotension, and organ failure.^[17]

Staphylococcal TSS

Staphylococcal TSS most commonly occurs in women, usually those who are using tampons. TSS develops within 5 days after the onset of menstruation. The other clinical settings where staphylococcal TSS has been reported include the following:

• Surgical wound infections
• Postpartum infections
• Focal cutaneous and subcutaneous lesions
• Deep abscesses
• Empyema
• Peritonsillar abscess
• Sinusitis
• Osteomyelitis

Approximately 20% of patients with staphylococcal TSS have an influenza-like syndrome characterized by the following:

• Fever
• Chills
• Myalgia
• Nausea
• Vomiting
• Diarrhea

The other reported types of infection are pneumonia, unidentified bacteremia, surgical site infection, septic arthritis, thrombophlebitis, meningitis, pelvic infection, and endophthalmitis.

The following risk factors have been reported to be associated with  staphylococcal TSS:

• Patients with HIV, diabetes, cancer, ethanol abuse, and other chronic diseases
• Patients with a recent history of varicella infection (chicken pox)
• Patients who used nonsteroidal anti-inflammatory drugs (NSAIDs)

Streptococcal TSS

Soft tissue infections from group A Streptococcus (GAS) include necrotizing fasciitis, myositis, or cellulitis. The most common initial symptom of patients with streptococcal TSS is diffuse or localized pain that is abrupt and severe. Other manifestations include the following:

• Influenza-like syndrome
• Fever
• Confusion
• Signs of soft tissue infection

Common presenting symptoms and frequency of streptococcal TTS are as follows^[15] :

• Pain (44-85%)
• Vomiting (25-26%)
• Nausea (20%)
• Diarrhea (14-30%)
• Influenza-like symptoms (14-20%)
• Headache (10%)
• Dyspnea (8%)

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Physical Examination

Fever is the most common presenting sign, although patients in shock may present with hypothermia. Shock is apparent at the time of hospitalization or within 4-8 hours for all patients. Patients become severely hypotensive and do not respond to intravenous fluid administration. Renal dysfunction progresses or persists in all patients, precedes shock in many patients, and is apparent early. Acute respiratory distress syndrome occurs in over half of patients.

A thorough search for possible sites of streptococcal and staphylococcal infection is important. The surgical wounds should be carefully examined even if no signs of infection are apparent. Vaginal examination and removal of tampon or other foreign body should be done diligently.

Confusion is common, and coma or agitation may occur. Alteration in mental status disproportionate to the degree of hypotension can occur with or without seizures. Persistent neuropsychiatric sequelae manifested by memory loss and poor concentration have been reported.

Approximately 80% of patients have clinical signs of soft tissue infection (eg, localized swelling, erythema), which usually progresses to necrotizing fasciitis or myositis.

Approximately 20% of patients have various clinical presentations, including the following:

• Endophthalmitis
• Myositis
• Perihepatitis
• Peritonitis
• Myocarditis

Diffuse scarlatina-like erythema occurs in 10% of patients. Skin manifestations of streptococcal infection include the following (also see images below):

• Bullae
• Scarlet fever–like rash
• Petechiae or maculopapular rashes
• Desquamation

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Progression of soft tissue swelling to vesicle or bullous formation is an ominous sign and suggests streptococcal shock syndrome. Courtesy of S. Manoc....

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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. This patient also had streptococcal pharyngitis. Co....

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A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock syndrome. The patient had diffuse erythroderma, a characteris....

Mucosal involvement includes conjunctival/scleral hemorrhage and hyperemia of the vaginal and oropharyngeal mucosa. Petechial hemorrhages (“strawberry tongue”) and ulcerations of mucosal membranes can occur in severe cases. 

The possibility of staphylococcal TSS should be considered in any patient who presents with a sudden onset of fever, rash, and hypotension. 

Common presenting symptoms and frequency of streptococcal TTS are as follows^[7] :

• Tachycardia (80%)
• Fever (70-81%)
• Hypotension (44-65%)
• Confusion (55%)
• Localized erythema (44-65%)
• Localized swelling and erythema (30-75%)
• Scarlatiniform rash (0-4%)

The case definition of streptococcal TSS involves the isolation of GAS, hypotension, and multisystem involvement.^[18]

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Complications

Severe complications from streptococcal TSS include the following^[7] :

• Prolonged and refractory hypovolemic shock (95%)
• Acute respiratory distress syndrome (55%)
• Acute kidney injury (reversible in 70%, irreversible 10%)
• Bacteremia (60%)
• Electrolyte and acid-base imbalance
• Cardiac dysrhythmia
• Thrombocytopenia
• Disseminated intravascular coagulation

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Laboratory Studies

CBC count with differential should be performed to determine the following:

• Leukocytosis with a polymorphonuclear shift to the left
• Mild leukocytosis with significant immature neutrophils on peripheral smear

Urinalysis should be performed to determine the following:

• Myoglobinuria and hemoglobinuria present
• Sterile pyuria

Prolonged prothrombin and activated partial thromboplastin times should be obtained.

Serum biochemistry to determine the following:

• Serum creatinine - Frequently elevated and precedes the development of hypotension in 50% of cases
• Hypoglycemia
• Low serum protein and albumin concentrations
• Elevated blood urea nitrogen
• Elevated transaminases
• Elevated bilirubin and creatine phosphokinase levels
• In myositis or necrotizing fascitis, elevated serum creatinine kinase concentration

Blood cultures to determine the following:

• Blood cultures positive for bacteria - Present in approximately 60% of the cases of disease associated with GAS
• Compared with STSS, blood cultures rarely positive for staphylococci

Gram stain and cultures to determine the following:

• S aureus - Identified easily by Gram stain and culture from a well-defined focus of infection (eg, abscess, wound infection)
• In cases associated with menstruation, as many as 90% of patients demonstrate the organism in cultures from the cervix or vagina, in the absence of clinical infection
• S aureus bacteriemia - Uncommon in patients with TSS

Common laboratory abnormalities in patients with streptococcal TSS include the following^[15] :

• Hypoalbuminemia (85%)
• Hypocalcemia (79%)
• Elevated liver transaminase levels (63%)
• Prolonged prothrombin time and/or activated partial thromboplastin time (60-71%)
• Elevated creatinine level (40-89%)

The case definition of streptococcal  toxic shock syndrome (TSS) involves (1) the isolation of group A Streptococcus (GAS) from either a sterile body site or a nonsterile body site and (2) a determination the clinical severity based on whether hypotension is present and the presence/absence of the following clinical and laboratory abnormalities:

• Renal impairment
• Coagulopathy
• Liver abnormalities
• Acute respiratory distress syndrome
• Extensive tissue necrosis (ie, necrotizing fasciitis)
• Erythematous rash

A definite case of TSS is defined as isolation of GAS from a sterile site and hypotension plus two or more of the clinical and laboratory abnormalities.

A probable case of TSS is defined as isolation of GAS from a nonsterile body site and hypotension plus two or more of the clinical and laboratory abnormalities.

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Imaging Studies

Imaging studies include the following:

• Chest radiography
• CT scan and/or ultrasound scan of potential focus of infection

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Medical Care

Toxic shock syndrome (TSS) has a rapid, dramatic, and fulminant onset. Quick recognition of the syndrome is important for enabling appropriate and prompt treatment. S pyogenes continues to be susceptible to beta-lactam antibiotics. Although very effective in treating pharyngitis and other superficial infections, aggressive group A Streptococcus (GAS) infections do not respond well to penicillin and continue to be associated with high mortality rates and extensive morbidity.

The principles in the management of septic shock in general must be instituted as soon as possible (see Septic Shock). These include the following components:

• Early recognition
• Early and adequate antibiotic therapy
• Source control and early debridement of infected/necrotic wounds
• Early hemodynamic resuscitation and continued support
• Corticosteroids (refractory vasopressor-dependent shock)
• Tight glycemic control (glucose target of < 180 mg/dL is considered to be adequate based on present data)
• Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS) with maintenance of plateau pressures of less than 30 cm of water

The combination of clindamycin and beta-lactam antibiotics may be associated with improved outcomes. Clindamycin may have better tissue penetration than beta-lactam antibiotics, may enhance phagocytosis of pathogens, and may inhibit bacterial superantigen production.

Penicillin and other beta-lactam antibiotics are most efficacious against rapidly growing bacteria; therefore, these antibiotics have the greatest efficacy when organisms are growing rapidly during the early stages of infection or in mild infections. When higher concentrations of GAS accumulate (eg, deep-seeded infections), the effectiveness of beta-lactam antibiotics decreases because the bacterial growth slows (stationary phase).

Penicillin mediates its antibacterial action against GAS by interacting with penicillin-binding proteins (PBPs). Experimentally, the binding of penicillin has been shown to decrease in stationary cells, related to cells in the logarithmic growth phase; thus, the loss of certain PBPs during the stationary growth phase may be secondary to the inoculum effect and may account for penicillin failure.

Clindamycin has multiple effects against GAS infection. The efficacy of clindamycin is not affected by inoculum size or growth stage; furthermore, this agent is a potent suppressor of bacterial toxin synthesis. Clindamycin facilitates phagocytosis of GAS by inhibiting M protein synthesis. Clindamycin suppresses synthesis of PBPs, which also are enzymes involved in cell wall synthesis. Clindamycin has a longer postantibiotic effect than penicillin. Clindamycin causes suppression of lipopolysaccharide-induced monocyte synthesis of TNF.^[20]

Dixit et al reported successful treatment of a case of recurrent menstrual TSS after tampons were discontinued with rifampicin and clindamycin.^[21]

The FDA approved three newer antibiotics, oritavancin (Orbactiv), dalbavancin (Dalvance), and tedizolid (Sivextro), for the treatment of acute bacterial skin and skin structure infections. These agents are active against Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MSSA, MRSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), among others. For complete drug information, including dosing, see the following monographs:

• Oritavancin
• Dalbavancin
• Tedizolid

Most patients who develop TSS are critically ill and should be transferred to an intensive care unit of an institution capable of caring for these patients.

Recommended antibiotic therapy

The administration of empiric broad-spectrum beta-lactam antibiotics in addition to clindamycin or linezolid (as antitoxin) is recommended.

Vancomycin can be used in penicillin-allergic patients.

Intravenous fluids

TSS causes refractory hypotension and diffuse capillary leak; therefore, judicious and even large-volume intravenous fluid resuscitation and invasive hemodynamic monitoring may be necessary.

The patient's blood pressure may improve with administration of fluids alone; otherwise, vasopressors will be needed to restore adequate tissue perfusion.

Patients with TSS will require supportive measures, including intubation and mechanical ventilation, dialysis in patients who have developed renal failure, and adequate nutritional support.

Other treatment measures

Intravenous immunoglobulin

Although intravenous immunoglobulin (IVIG) therapy in TSS has been suggested, there is no clear clinical evidence to support its use in this setting.

Several retrospective observational studies have reported conflicting results of the effect of IVIG on mortality.^{[22, 23, 24, 25]}

A multicenter, randomized, double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS). The trial was terminated due to slow patient recruitment. Although no conclusion can be drawn from the results, there was a decrease in the sepsis-related organ failure in the IVIG group.^[26]

Another randomized placebo-controlled study evaluated the effect of IVIG in necrotizing soft tissue infection and did not demonstrate mortality benefit.^[27]

The administration of IVIG as an adjunctive treatment for TSS requires further evaluation.

Others

Hyperbaric oxygen has been used anecdotally in few patients, but whether this treatment is useful is not clear.

High-dose corticosteroid therapy has not been shown to be beneficial. Stress-dose steroids (hydrocortisone 50 mg IV every 6 hours) may be considered in patients with septic shock despite adequate fluid resuscitation, antimicrobial theory, and source control.

Research is continuing to develop either monoclonal antibodies against TSST-1 or other peptides to block the ability of bacterial toxins to activate T cells, therefore blocking the toxicity cascade.^[28] Most of this research is focused on in vitro and animal models of toxic shock.

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Surgical Care

A deep-seeded pyogenic infection constitutes a surgical emergency, and prompt, aggressive exploration and debridement of infected tissue is strongly indicated. Surgical exploration through a small incision with visualization of the muscle and fascia may provide an early and definitive diagnosis of necrotizing fasciitis. Infection often is more extensive than is apparent from external examination. Surgical debridement of infected tissue is extremely important and often requires re-exploration to ensure adequacy of resection.

See the images below.

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Extensive debridement of necrotizing fasciitis of the hand.

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The hand is healing following aggressive surgical debridement of necrotizing fasciitis of the hand.

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Consultations

Consultation with a surgeon should occur early.

A consultation with an infectious diseases specialist is mandatory, and a consultation with an intensivist also is required for management of these patients in an intensive care unit.

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Prevention

Patients who recover from TSS are at risk of recurrent episodes of STSS. Consider or recommend preventive therapy (eg, discontinuation of tampon usage, administration of antistaphylococcal antibiotics) before and during each menstrual period for several months.

Chemoprophylaxis of household contacts of STSS patients: Household contacts of people with STSS have a higher risk of invasive GAS infection compared to the general population. The Centers for Disease Control and Prevention have not made definite recommendations; some authors have recommended a 10-day course of cephalosporin.

Patient education about early signs and symptoms, risk factors, and avoidance of tampon use may help prevent relapses.

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Guideline Summary

The CDC has issued clinical guidance for the treatment of streptococcal TSS. The key recommendations are summarized below.^[29]  

• Hospitalization is required. Standard treatment of shock and organ failure, such as fluid resuscitation, is imperative as the first step in treatment.
• When sepsis is suspected, start antibiotics as soon as possible, and other needed therapies. reassess antibiotics within 24-48 hours and stop or change therapy as needed.  Antibiotics should be tailored once the diagnosis of streptococcal TSS is confirmed.
• Surgical debridement of deep tissue infection may be necessary.
• Early in the clinical course of severely ill patients, consider the use of intravenous immunoglobulin. 

The Infectious Diseases Society of America updated their guidelines for the diagnosis and management of skin and soft tissue infections. For the full guidelines, see Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.^[30]

Additional guides from the Surviving Sepsis Campaign Committee have also been updated. See Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2021.^[31]

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Medication Summary

The goals of pharmacotherapy are to reduce morbidity, prevent complications, and eradicate the infection. The FDA approved three newer antibiotics, oritavancin (Orbactiv), dalbavancin (Dalvance), and tedizolid (Sivextro), for the treatment of acute bacterial skin and skin structure infections. These agents are active against Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MSSA, MRSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), among others. For complete drug information, including dosing, see the following monographs:

• Oritavancin
• Dalbavancin
• Tedizolid

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Clindamycin (Cleocin, Cleocin Pediatric, Clindamax)

• Dosing, Interactions, etc.

Clinical Context:  Clindamycin is a lincosamide indicated for serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). As much as 20% of group B streptococci may be resistant. Clindamycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

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Penicillin G aqueous (Pfizerpen, Crystapen, Penicillin G potassium)

• Dosing, Interactions, etc.

Clinical Context:  Aqueous penicillin G interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

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Nafcillin (Nafcil, Nallpen)

• Dosing, Interactions, etc.

Clinical Context:  Nafcillin is initial therapy for suspected penicillin G–resistant staphylococcal infections. Use parenteral therapy initially in severe infections. Owing to thrombophlebitis, particularly in elderly patients, administer parenterally only for the short term (1-2 d); change to oral route as clinically indicated.

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Vancomycin (Firvanq, Vancocin)

• Dosing, Interactions, etc.

Clinical Context:  Vancomycin is a potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Vancomycin is useful in the treatment of patients with septicemia and skin structure infections. It is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci (eg, MRSA). For abdominal penetrating injuries, combine with an agent active against enteric flora and/or anaerobes.

Use creatinine clearance to adjust dose in patients with renal impairment.

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Oxacillin (Bactocill)

• Dosing, Interactions, etc.

Clinical Context:  Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci. Oxacillin may be used to initiate therapy when staphylococcal infection is suspected.

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Tedizolid (Sivextro)

• Dosing, Interactions, etc.

Clinical Context:  Tedizolid is an oxazolidione antibiotic; its action is mediated by binding to the 50S subunit of the bacterial ribosome, resulting in inhibition of protein synthesis.

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Oritavancin (Kimyrsa, Orbactiv)

• Dosing, Interactions, etc.

Clinical Context:  Oritavancin is a lipoglycopeptide antibiotic that exerts concentration-dependent bactericidal activity.

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Dalbavancin (Dalvance)

• Dosing, Interactions, etc.

Clinical Context:  Dalbavancin is a lipoglycopeptide antibiotic; it interferes with cell wall synthesis by binding to D-alanyl-D-alanine terminus of the stem pentapeptide in nascent cell wall peptidoglycan, thus preventing cross-linking.

Dalbavancin is bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations observed in humans at recommended doses.

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Class Summary

Antimicrobial therapy must cover all likely pathogens in the context of the clinical setting.

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